DIET AND LIVER METABOLISM DETERMINE BRAIN METABOLISM OF NUTRITIONALLY ESSENTIAL POLYUNSATURATED FATTY ACIDS[unreadable] A coherent mathematical model, based on experimental studies in rodents, showed how brain composition and metabolism of the polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and arachidonic acid (AA), are regulated by their dietary intake and/or liver synthesis from their respective PUFAs, alpha-linolenic acid (alpha-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6). In the absence of dietary DHA, but with sufficient dietary alpha-LNA (4.5% of total fatty acids), the rat liver can maintain a normal brain DHA content by synthesizing 5-10 times more DHA than the brain consumes. Rates of incorporation of circulating DHA and AA into brain, determined with quantitative autoradiography in unanesthetized rodents and with positron emission tomography (PET) in humans, equal respective rates of consumption within brain. The adult human brain consumes AA and DHA at rates of 17.8 and 4.6 mg/day, respectively. AA consumption does not change significantly with human aging (Rapoport et al. 2007a, Rapoport et al. 2007b).[unreadable] [unreadable] DIETARY N-3 PUFA DEPRIVATION UPREGULATES ELONGASES AND DESATURASES IN RAT LIVER BUT NOT BRAIN[unreadable] Estimated synthesis-secretion coefficients of docosahexaenoic acid (DHA) from circulating unesterified alpha-linolenic acid (alpha-LNA) were higher in liver than brain in rats fed an adequate alpha-LNA diet, and were further upregulated in liver but not brain by 15 weeks of dietary n-3 polyunsaturated fatty acid (PUFA) deprivation. The diet induced elevation in the hepatic coefficients reflected increased mRNA and activity levels of enzymes that convert alpha-LNA to DHA, namely delta-5 and delta-6 desaturases and elongases 2 and 5. Thus, the rat liver responds to dietary n-3 PUFA deprivation by increasing transcription of enzymes that convert alpha-LNA to DHA, and upregulating its conversion capacity (Igarashi et al. 2007).[unreadable] [unreadable] HEART CAN'T SYNTHESIZE DOCOSAHEXAENOIC ACID FROM CIRCULATING ALPHA-LINOLENIC ACID BECAUSE IT LACKS ELONGASE-2[unreadable] Dietary supplementation with long-chain polyunsaturated fatty acids (PUFAs), including DHA, reduces the incidence of sudden cardiac death. The rat heart, however, cannot convert alpha-linolenic acid (18:3n-3) to longer-chain DHA (22:6n-3) because it lacks a critical enzyme, elongase 2. It must obtain its DHA entirely from dietary sources or by liver synthesis from alpha-LNA. Dietary n-3 PUFA deprivation in the rat reduces heart DHA and increases heart docosapentaenoic acid (22:5n-6), which may increase vulnerability to ischemia (Igarashi et al. 2008).[unreadable] [unreadable] FATTY ACID COMPOSITION OF WILD ANTHROPOID PRIMATE MILK[unreadable] Anthropoid primates vary in growth, development and brain size. In collaboration with scientists at the National Zoo, we found that milk from leaf eating species had a higher proportion of alpha-linolenic acid (18:3n-3) than did milk from omnivores. Mountain gorillas had a uniquely high proportion of milk arachidonic acid (20:4n-6). The differences were unrelated to brain size, and reflected species metabolic differences and/or differences in diet (Milligan et al. 2008).